X-ray diffraction techniques will be used to investigate the structure of histidine decarboxylase from Lactobacillus 30Alpha. This is a bacterial amino acid decarboxylase found in mammalian intestines which produces the important neurotransmitter histamine and possesses a number of unique properties. Enzyme activation occurs when a pyruvoyl moiety is formed from an internal serine residue of proenzyme pi subunit. Unlike most other amino acid decarboxylases, this covalently bound pyruvoyl residue is utilized in the active site instead of pyridoxal-5'-phosphate. Our preliminary electron microscopy and ultracentrifugation results establish that the proenzyme has the subunit composition (Pi)6. The native enzyme is a dumbbell shaped particle of molecular weight about 208,000. It has an (AlphaBeta)6 subunit composition and possesses 32 molecular symmetry. Several crystal forms of histidine decarboxylase have been obtained under various conditions. A tetragonal form of the wild-type enzyme and isomorphous trigonal forms of proenzyme and activated proenxyme have been selected for crystallographic analysis. Isomorphous heavy atom derivatives have also been obtained. We propose to continue our characterization of this unique system by determining the three dimensional structures of these enzymes. These structural studies represent the first such investigations of a keto acid dependent enzyme and will aid in understanding their mechanism of catalytic action and proenzyme activation.